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PKPD II > Exam 1 > Flashcards

Exam 1 Flashcards

1
Q

Lecture 1: Genetics

Goals of product label

A

ensure consistency
provide clarity
general information framework
emphasizes variability measures

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2
Q

Lecture 1: Genetics

Forest plot

A

the greater the confidence length, the more significant the factor i sin terms of disturbing the drug

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3
Q

Lecture 1: Genetics

cmax and Auc higher in males or females?

A

females

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4
Q

Lecture 1: Genetics

most important eq. in pk

A

Css= FxDose/ (Cltot x tau)

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5
Q

Lecture 1: Genetics

most major clearance mechanisms in order

A
  1. metabolism
  2. renal
  3. bile1
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6
Q

Lecture 1: Genetics

most major metabolic mechanisms for clearance

A
  1. CYP
  2. UGT
  3. esterase
  4. other
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7
Q

Lecture 1: Genetics

most major cyp mechanisms

A
  1. cyp3a
  2. CYP2C9
  3. CYP2D6
  4. CYP2C19
  5. CYP1A
  6. CYP2E1
  7. CYP2B6
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8
Q

Lecture 1: Genetics

What is central tendency and variation

A

central tendency measure (mean exposure ) btw 2 specific populations (ex: w. and w.o hepatic impairment)

variability: variability in oboe measures

PKPK values should be reported as mean(arithmic or geometric) or median with measure of dispersion (standard of deviation and/or max and min values)

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9
Q

Lecture 1: Genetics

Box and whisper plot

A

bar in the middle is the median

t

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10
Q

Lecture 1: Genetics

variance

A

measures of the deviation of observers from the mean

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11
Q

Lecture 1: Genetics

standard deviation

A

average deviation of observations from the mean

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12
Q

Lecture 1: Genetics

coefficient variation

A

the standard deviation normalized to the mean.

CV= SD/mean

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13
Q

Lecture 1: Genetics

intersubject variation

A

btw 2 patients

high is above 30% cv

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14
Q

Lecture 1: Genetics

intrasubject variation

A

in one pt

low is below 30%
medium is 30-60%
high is above 60%

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15
Q

Lecture 1: Genetics

which drugs tend to have higher variability?

ones with low bioavailability (F) or high F?

A

low bioavailability

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16
Q

Lecture 1: Genetics

Pristiq (DEsvenlafaxine) variability

A

has low variability

Coefficient variant (CV)<30 % means there is low variability

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17
Q

Lecture 1: Genetics

For central tendency, does tmax use mean or median?

A

median

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18
Q

Lecture 1: Genetics

spaghetti plot

A

shows variability in lines of all pts

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19
Q

Lecture 1: Genetics

histogram

A

emphasizes skewed distribution

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20
Q

Lecture 1: Genetics

crestor (rosuvastatin) genetic varibaility

A

asian subjects have higher plasma concentrations after standard doses of the drug.

recommend lower dose in asians

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21
Q

Lecture 1: Genetics

propanolol

A

white ppl needed twice as high conc. to recieve the same amount of beta blockade as asians .

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22
Q

Lecture 1: Genetics

which enzyme causes for greatest variability

A

CYP2D6

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23
Q

Lecture 1: Genetics

how is pristiq (desvenlafaxine) primarily metabolized

A

primarily by conjugation budgeted by UGT and to a minor extent by CYP3A4 (basically primarily eliminated by metabolism)

not metabolized by

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24
Q

Lecture 1: Genetics

metabolic ratio equation.
what does it mean?
Is it a true pk parameter

A

metabolic ration=Drug/OHD metabolite

high ratio: … more drug, less metabolite

not a true pk parameter

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25
Q

Lecture 1: Genetics

examples of drugs subject to genetic variability in pk because od cyp2d6

A

DEBRISOQUINE, METOPROLO, ENCAINAMIDE, IMIPRAMINE, NORTRIPTYLINE, MAPROTILINE, ETC.

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26
Q

Lecture 2: Age and Weight

as age increases, percentage of no prescription drug use increases or decreases?

A

decreases

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27
Q

Lecture 2: Age and Weight

what sex weighs more

A

males weigh more than female

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28
Q

Lecture 2: Age and Weight

clearance values corrected for body size

A

look at the units of clearance to see if it has been adjusted for body size.

gives a better understanding of the pk parameter

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29
Q

Lecture 2: Age and Weight

what age does CL peak

A

around 2-3 years old, at max capability.

then, it decreases 1% per year

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30
Q

Lecture 2: Age and Weight

what is the average adult weight

A

male: 70 kg-1.73 m^2

female ~ 60 kg

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31
Q

Lecture 2: Age and Weight

allometric scaling

A

body functions change in proportion to body weight by a power function,

CL: ax BW^0.75 (can range depending on drug)

vd: A X BW^ 1.0

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32
Q

Lecture 2: Age and Weight

Calculation of BSA

A

approximation EQUATION

SA=0.1 BW^2/3 (kg)

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33
Q

Lecture 2: Age and Weight

diazepam changes in t 1/2

A

as age increased, t 1/2 increases, lower CL
males have higher t 1/2 then females
CL higher in older females than older males

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34
Q

Lecture 2: Age and Weight

effect of Vd and CL with age

A

with age, Vd increased because fat increases, and Cl decreases because kidney function decreases,, there for that joint effect creates longer t 1/2

t 1/2= (0.693 x V)/CL

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35
Q

Lecture 2: Age and Weight

age on Vd

A

as you get oder , gain more fat, so Vd increases, especially with drugs with higher lipophilicity. not so much in hydrophilic drugs

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36
Q

Lecture 2: Age and Weight

concentrations and EC50

A

aging patients are more sensitive to lower blood concentrations, which means they would not require as high as a dose as younger pts to reach the same effect.

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37
Q

Lecture 2: Age and Weight

aging and PD

A

aging effects on PD have been reported with increases and decreases in drug sensitivity. no clear trend may be anticipated

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38
Q

Lecture 2: Age and Weight

percent of total body weight of baby

A

water accounts for 80% in babies’TBW.

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39
Q

Lecture 2: Age and Weight

changes in metabolic activity

A

newborns have very limited metabolic activity. don’t metabolize drugs well

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40
Q

Lecture 2: Age and Weight

Cl and ec50 in neonates

A

neonates have lower CL, and therefor have lower ec50’s. means they are more sensitive to the drug

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41
Q

Lecture 2: Age and Weight

dosing of drugs for children < 2 year sold

A

dosing must be individualized for drugs at ages <2 years old.

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42
Q

Lecture 2: Age and Weight

equation for childs maintenance dose

A

1.5 x ((wt. (kg)child)/70)^0/75 x adult maintenance dose

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43
Q

Lecture 2: Age and Weight

pk pid of d- tubocurarine

A

neonates showed lower Cl, and thus had lower EC50’s then infants, children, and adults

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44
Q

Lecture 3: Role of Sex (gender) and chronobiology

difference in metabolism tendencies btw M and F..

CYP3A4
CYP2C19
CYP2D6
CYP1A2

A

cyp3a4: F>M
cyp2c19: F=M
Cyp2d6: F

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45
Q

Lecture 3: Role of Sex (gender) and chronobiology

methylprednisolone is met. by cyp3a4. which sex metabolizes faster?

A

F>M

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46
Q

Lecture 3: Role of Sex (gender) and chronobiology

cortisol circadian rhythms

A

women had a lower IC50, meaning they are more sensitive to adrenal suppression.

net response is the same

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47
Q

Lecture 3: Role of Sex (gender) and chronobiology

metoprolol and cyp2d6 metabolism

A

men have higher clearances, so would require more drug.

no differences in PD

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48
Q

Lecture 3: Role of Sex (gender) and chronobiology

quinidine and cyp3a4

A

women were faster metabolizers

women had greater qt elongation (an AE of the drug)

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49
Q

Lecture 3: Role of Sex (gender) and chronobiology

seldane (terfenadine)

A

was toxic to women because seldane has an interaction with ketoconazole. cause huge qt prolongation. causing tornadoes des pointes. leading to death

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50
Q

Lecture 3: Role of Sex (gender) and chronobiology

aspirin

A

women have less stroke prevention, even though decrease of platelet aggregation was the same

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51
Q

Lecture 3: Role of Sex (gender) and chronobiology

effect of pregnancy on pK

A

increased cL: heparin, nifedipine

decreased cL: theophylline, caffeine (both cyp1a substrates)

some no effect: overall, unpredicatable PK differences in pregnancy

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52
Q

Lecture 3: Role of Sex (gender) and chronobiology

heparin in pregnancy

A

increase cL, decreased response

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53
Q

Lecture 3: Role of Sex (gender) and chronobiology

COC users and theophylline

A

drugs that are cyp metabolized have reduced clearance in women taking COC’s

cons cause metabolic inhibition. (or decreased clearance)

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54
Q

Lecture 3: Role of Sex (gender) and chronobiology

COC users and tizanidine

A

greater conc. because of cyp1a2 inhibition od coc’s

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55
Q

Lecture 3: Role of Sex (gender) and chronobiology

COC users and most conjugation enzymes

ex: lorazepam

A

increased clearance due to induced conjugation by coc

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56
Q

Lecture 3: Role of Sex (gender) and chronobiology

circadian rhythm

A

over 24 hours

ADME can change depending on the time of day

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57
Q

Lecture 3: Role of Sex (gender) and chronobiology

circadian rhythm and renal function

A

GFR is 20-30% higher during the day than at night.

many drugs show reduced Clr at night

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58
Q

Lecture 3: Role of Sex (gender) and chronobiology

circadian rhythm and 5FU

A

plasma conc were higher at night because of reduced decreased enzyme activity at night

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59
Q

Lecture 3: Role of Sex (gender) and chronobiology

propanolol

A

plasma conc during the day were high, produced in a good % decreased heart rate, however, when given propranolol at night, the conc were very low, but the response was the same as propranolol given in the day

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60
Q

Lecture 3: Role of Sex (gender) and chronobiology

diastolic bp with valsartan

A

if valsartan is dosed during the day, higher drops of diastolic bp occur than if the valsartan is dosed at night

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61
Q

Lecture 3: Role of Sex (gender) and chronobiology

diseased and circadian rhthms

A

some diseases are exacerbated at certain times of the day.

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62
Q

Lecture 3: Role of Sex (gender) and chronobiology

bio markers and circadian rhythms

A

cortisol: peaks in morning
melatonin: peaks at night
serum IL-6: go up during early morning.

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63
Q

Lecture 3: Role of Sex (gender) and chronobiology

acrophase

A

the peak

64
Q

Lecture 3: Role of Sex (gender) and chronobiology

circatrigintan rhythm

A

female menstruation rhythm

over a 28 day period

65
Q

Lecture 4: Role of food and Obesity

Theo-24 (theophylline 1500 mg) single dose

A

theophylline dose usually 500 mg tid. however when theo-24 was used, after r breakfast, it caused a drug release during the food regimen (dose dumping) pt got nausea, repeated vomiting, or severe throbbing headache

66
Q

Lecture 4: Role of food and Obesity

what is a food effect study

A

give drug with empty stomach and then with food (high fat) and look at pk

67
Q

Lecture 4: Role of food and Obesity

food effect with tizanidine

A

food decreased plasma concentrations of tizanidine when taken in a capsule dosage form

68
Q

Lecture 4: Role of food and Obesity

FDA and food effect study requirements

A

no food effect if 90% of Cl of fed/fasted Cmax and AUC rations within 80-125%

69
Q

Lecture 4: Role of food and Obesity

desvenlafaxine

A

food study showed that there is no food effect

70
Q

Lecture 4: Role of food and Obesity

possible food effects on drug absorption

A

delayed gastric emptying

stimulated bile flor

changed gi pH

increased splanchnic (GI) blood flow

altered luminal metabolism/ transport of drugs

physically or chemically interact with the dosage form or drug substance (degradation in acidic stomach)

71
Q

Lecture 4: Role of food and Obesity

food effect on gastric emptying

A

food decreases gastric emptying

72
Q

Lecture 4: Role of food and Obesity

grapefruit

A

grapefruit contains furanocoumarins, which inactivate GI cyp3a4. loss of first pass effect in the intestine, causing higher concentrations

ex: grapefruitt and simvastatin

how long does it take: ~3 days, but completely about a week

73
Q

Lecture 4: Role of food and Obesity

vitamins

A

vitamins should always be taken with food. absorbed better

74
Q

Lecture 4: Role of food and Obesity

are drug studies required for obese ppl by the FDA ?

A

no

75
Q

Lecture 4: Role of food and Obesity

causes of obesity

A

primary causes: genetic, monogenic, syndromes

76
Q

Lecture 4: Role of food and Obesity

BMI

A

BMI equation: weight (kg)/Ht (m^2)

normal bmi= 19-24
pre obesity: 25-29.9
obesity class I. 30-34.9obesity class II: 35-39.9
obesity class III: 40+
77
Q

Lecture 4: Role of food and Obesity

body adiposity index (bai)

A

measure body fat

78
Q

Lecture 4: Role of food and Obesity

CCl in obesity

CrCl equations for weight

A

slightly greater in obesity than in ppl with normal weights. kidneys work better because they are struggling to get water out of obese subject, so they work harder

Salazaar equations:

male: [137-age]x[0.285xwt)+(12.1xht^2)]/ (51x Scr)
female: [146-age]x[0.287xwt)+(9.74xht^2)]/ (60x Scr)

79
Q

Lecture 4: Role of food and Obesity

methods of measurementt of %fat or ibw

A

skin fold calipers

bioimpedence: electric shock through body that can measure % body weight (like a bathroom scale)

estimation of IBW by equations

80
Q

Lecture 4: Role of food and Obesity

drug absorption

A

no change in drug absorption in obese

81
Q

Lecture 4: Role of food and Obesity

total clearances of compounds eliminated primarily by renal excretion

A

obesity is accompanied by partial increases in renal function.

account for partial increase is using adjusted body weight

ABW= IBW +0.4 (tbw-ibw)

82
Q

Lecture 4: Role of food and Obesity

volume of distribution

A

VD depends on lipophilicity Fat and degree of obesity (vfat)

83
Q

Lecture 4: Role of food and Obesity

thiopental in obese pts

A

cl is difference, but when adjusted for body weight, cl is the same

t 1/2 is larger due to larger Vd and larger log p

thiopental has a logp=3.52, which means it is lipophyllic

84
Q

Lecture 4: Role of food and Obesity

volume of distribution for hydrophilic drugs

A

vd is about the same

85
Q

Lecture 4: Role of food and Obesity

metabolic cl in obese

A

unpredicatable. anything can happen. (increase, decrease, constant, enhanced)

reduced cl can happen with some drugs due to obese liver

86
Q

Lecture 4: Role of food and Obesity

methylprednisolone conc. in obese

A

steroid con. increases

however ic50 for cortisol suppression is not different

87
Q

Lecture 4: Role of food and Obesity

conjugation in obesity

A

enhanced glucuronide conjugation in obesity. cl most likely to increase for jugs which are conjugated

88
Q

Lecture 4: Role of food and Obesity

lithium Cl in obese

A

lithium is hydrophilic and mainly excreted by kidneys.

lithium may need larger doses due to increase CrCl in obese ppl

89
Q

Lecture 4: Role of food and Obesity

verapamil and atracurium in obesity

A

both show increased ec50 with obesity, meaning less sensitivity

90
Q

Lecture 5: smoking

primary effect of tobacco on drugs

A

induction of hepatic microsomal enzymes

91
Q

Lecture 5: smoking

theophylline and smoking

A

smokers had exaggerated increase in cL

92
Q

Lecture 5: smoking

thiocyanate

A

metabolic product of cyanide which is found in tolerance

93
Q

Lecture 5: smoking

2nd hand smoking

A

passive exposure was to environmental cigarette smoke for atleast 4 hours a day .

saw increases in plasma cotinine (metabolite of nicotine) as well increased Cl

94
Q

Lecture 5: smoking

probable causative compounds for enzyme induction

A

carcinogenic polycyclic hydrocarbons

95
Q

Lecture 5: smoking

propanolol

A

metabolized by 2d6. marked decrease in plasma concentration.

enzyme induction more prominent in younger ppl than older ppl

96
Q

Lecture 5: smoking

tizanidine

A

the effects of tizanidine on bp pressure were weaker in smokers

97
Q

Lecture 5: smoking

trends

A

mostly unpredictable, but cyp1a substrates are more predictable, but no really

98
Q

Lecture 5: smoking

coc and smoking

A

cigarettes increase risk of serious cv effects and potential death

99
Q

Lecture 5: smoking

impotence

A

smoking increases impotence in men

100
Q

Lecture 5: smoking

vitamin use

A

smokers need more vitamins to have the same serum conc. of non smokers

101
Q

Lecture 5: smoking

OTCs drug use

A

smokers need and use more OTCs

102
Q

Lecture 5: smoking

smokers face

A

lines or wrinkles
giantess
atrophic grey appearance
plethoric blue, bloated appearance

103
Q

Lecture 5: smoking

time of enzyme induction in smoking

A

enzyme induction is slow (3 days to a week).

also a slow process to return back to normal

104
Q

Lecture 5: enzyme induction

compounds concerned for enzyme induction and what enzymes they induce

tobacco
rifampin
COC
anticonvulsants
st johns wort
ompeprazole
ethanol
hiv protease inhibitors
A

a. various
b. various
c. conjugation
d. cyp3a4
e. cyp3a4
f. cyp1a2
g. cyp2e1
h. various

105
Q

Lecture 5: smoking

st johns wort and alprazolam

A

st johns wort lowers concentration

chronically increases drug metabolism

106
Q

Lecture 5: enzyme induction

pkpd model for enzyme induction

A

ksyn->CYP3A4-> kdeg

107
Q

Lecture 5: smoking/ inducers

fda guidance on inducer

what are condiered strong inducers

moderate

weak

A

all new drugs should undergo cell structuree screening for causation of enzyme induction

strong: >80%
moderate: 50-80%
weak: 20-50%

108
Q

Lecture 5: smoking/ induction

fda guidance which enzymes sensitive to enzyme induction

A 
cyp1a2
cyp2b6
cyp2c8
cyp2c9
cyp3a4

CYP2D6 NOT SHOWN TO BE SENSITIVE TO ENZYME INDUCTION

109
Q

Lecture 6: Hepatic disease

hepatic diseases

A

liver cirrhosis:
characterized by over of fibrosis, reduced blood flor, reduced number of active hepatocytes, and impaired albumin ptoduction

Liver cholestasis: below flow from liver to duodenum is hindered, retention of substances normally excreted by bile

hepatitis and primary liver cancer:

110
Q

Lecture 6: Hepatic disease

child pugh score criterias

and score categories

A

encephalopathy:

ascites

bilirubin

albumin
prothrombin time

class a=5-6 points (least sever liver disease)

class b= 7-9 (moderately sever liver disease)

class c =10-15(most sever liver disease)

111
Q

Lecture 6: Hepatic disease

effect of liver disease on metabolism

A

radiation in absolute liver cell mass, decrease in enzyme activity

drug uptake in certain cells is impaired

decrease metabolism

112
Q

Lecture 6: Hepatic disease

hepatic enzymes effects from liver disease

A

cyp2e1: heavily influenced by liver disease

113
Q

Lecture 6: Hepatic disease

biliary nd renal excretion

A

in pts with chronic liver disease, dosage modification is not only necessary for drugs predominantly cleared by liver, but may also be indicated for renal cleared drugs

drugs and metabolites excreted by bile can accumulate

also cirrhotics have reduced renal plasma flow and GFR

114
Q

Lecture 6: Hepatic disease

general guidelines for optimization of dosing regimen for hepatic diseasepts.

A

reduction in dose or increase in dosing interval

115
Q

Lecture 6: Hepatic disease

High vs low Cl (extraction ) drug

A

high Cl drugs: Cl=Qh (he fastest the ever can metabolize is = to blood flow).
high cl drugs are relative insensitive to changes in drug binding or enzyme transporter activity

Low cl drugs: fu x Clint.

116
Q

Lecture 6: Hepatic disease

hepatic drug cl and bioavailability

A

h cl drug: lower f, which is very sensitive to changes in drug binding and intrinsic clearance

low cl drug: have higher f, which is less sensitive to changes in fu and intrinsic clearance

117
Q

Lecture 6: Hepatic disease

oral clearance vs iv clearance

A

if drug has high cl and given iv, cl=qh

all other situations ( low cl given iv, or high or low cl given orally ), cl= fu x clint

118
Q

Lecture 6: Hepatic disease

extent of absorption
F, bioavailability

A

oral bioavailability increases in absorption

ex: chlormethiazole

because you have decreased cl, you increase the bioavailability

119
Q

Lecture 6: Hepatic disease

effect on absorption rate

A

rate of absorption gets slowed down.

ex: furosemide, due to impaired gastric motility. cirrhosis pts are affected by gastritis and upper git ulcers, which may lead to delayed and unpredictable onset of action

120
Q

Lecture 6: Hepatic disease

protein binding and vd

A

decreased albumin production by liver in cirrhosis, as well as increased accumulation of endogenous compounds inhibiting plasma protein binding, and qualitative changes in albumin.

drugs that are highly protein bound have higher fu in cirrhosis and higher vd.

if dealing with a drug that has low vd, it does not matter how fu is changed,

if dealing with high vd drug, fu can significantly change the vd

121
Q

Lecture 6: Hepatic disease

total vs unbound concentration

A

cirrhosis can increase unbound concentrations,

however, it may not change total drug concentrations, because in the equation

css=dose/ (tau x fu x clint) , fu is going up, but clint is going down, keeping the total css appearing the same.

but b/c unbound conc drives pharmacologic effect, the increase in unbound conc can change the effects of the drug significantly without even realizing b/c the total conc is staying the same.

therefor, drug dosages still need to be changed.

Css u equations for oral and iv

oral: cuss= dose/ tau x clint

iv cuss: fu x dose/ q x tau

122
Q

Lecture 6: hepatic disease

css and cssu equations for oral and iv

A

oral:

css= dose/(tau x fu x clint)

cssu=dose /(tau x clint

iv: css= dose/ tau x Q

cssu= fu x dose/ tau x q

123
Q

Lecture 7: renal disease

how many L of filtrate does the kidney generate a day

how much urine does it generate a day

A

180 L

2L of urine a day

124
Q

Lecture 7: renal disease

assessment of renal function

A

Crcl: creatinine a by product of muscle metabolism that is primarily eliminated by glomerular filtration

eGFR

125
Q

Lecture 7: renal disease

Crcl units

A

overall Crcl would be in ml/min

make sure the SCr is in mg/dl

126
Q

common unit prefix conversions

A

10^-1: deci : (10)

10^-2: centi (100)

10^-3: milli (1000

10^-6: micro (1000000)

10^-9: nano (1000000000)

127
Q

Lecture 7: renal disease

when to use abw OR IBW

A

if the abw is less than the ibw, use abw in CRcl equation

if the pt is >65 yo ND SCR IS <1.0, USE 1 TO CALCULATE THE CRCL

if

128
Q

Lecture 7: renal disease

Crcl for obese patients

A

in obese pts, use actual weight. and the height in meters

1 METER=3.28 FT

if TBW is 30% more than ibw, then they are obese

129
Q

Lecture 7: renal disease

Crcl in children

A

independent weight formula

schwartz equation

130
Q

Lecture 7: renal disease

non steady state

A

to estimate Crclin non steady state situation, must measure Scr at 2 different points in time

131
Q

Lecture 7: renal disease

effect on absorption

A

small effects:

tmax can slightly increase

bioavailability can slightly increase

132
Q

Lecture 7: renal disease

effect and distribution

A

acidic drugs ( drugs that bind to albumin, are effected because increase in endogenous substances can decrease albumin, alter albumin, and displace drugs that bind to albumin. obverall increasing fu

basic drugs that bind to AAG protein may not be effected, however they might have a slightly lower fu because aaa is cleared through the kidney. high binding, lower fu.

133
Q

Lecture 7: renal disease

protein binding and vd

A

vd of a few drugs such as digoxin etc. can increase because of fluid overload in esrd due to increase in fluid overload

134
Q

Lecture 7: renal disease

effect on metabolism

A

non renal metabolism is effected by esrd because uremic toxins that accumulate can reduce drug metabolizing enzyme activity

however esrd can also effect phase II metabolism

135
Q

Lecture 7: renal disease

renal drug elmination

A

if renal function goes down, all cl mechanisms through the kidney will go down.

136
Q

Lecture 7: renal disease

fe: fraction excrete unchanged in urine and t 1/2

A

higher the value of fe, more pronounce the effect of renal failure on drug pk

137
Q

Lecture 7: renal disease

optimization of dosing regimens for renal disease

Detli rule 1:
kunin rule
Detli rule 2:

A
  1. rule 1: if keldepends linearly on gfr. if eel reduces by 1/2, reduces dose by 1/2, but keep the dosing interval

kunin rule 2:

start w. loading dose. then with every half life, give half the dose

Detli rule 2:
do not change dose level, instead, double the dosing interval.

138
Q

c0 equation

A

c0= dos/vd

139
Q

Lecture 8: endo/exo and other diseases

lidocaine and chi

A

increased conc due to decreased hepatic perfusion , decreasing liver metabolism of lidocaine

140
Q

Lecture 8: endo/exo and other diseases

pittsburg cocktail and chf

A

increase in pro inflammatory cytokines like tif a and il-6 can reduce metabolism of drugs

141
Q

Lecture 8: endo/exo and other diseases

vancomycin in chf

A

low clearance in chf

142
Q

Lecture 8: endo/exo and other diseases

thyroid diseases

hypo and hyper on ADME

A

HYPO
decrease ADME for the most part except increase serum albumin and agp

HYPER increase ADME for the most part except decrease serum albumin and agp

143
Q

Lecture 8: endo/exo and other diseases

prednisolone in hypethyroidism

A

decreased bioavailability due to increased gastric emptying

144
Q

Lecture 8: endo/exo and other diseases

antipyrine nd t1/2

A

hypo t, caused longer t1/2

145
Q

Lecture 8: endo/exo and other diseases

thyroid and renal cl

A

hyper increases grr and hypo decreases gfr

146
Q

Lecture 8: endo/exo and other diseases

cystic fibrosis ADME

A

A: absorption not impaired

D: reduced binding

M:many drugs exhibit enhanced clearances

e: many abx exhibit increased cl

147
Q

Lecture 8: endo/exo and other diseases

dicloxacillin in cystic fibrosis

A

has increased cl also decreased protein binding

148
Q

Lecture 8: endo/exo and other diseases

abx in cf

A

marked increase in cl, primarily cleared by kidneys

149
Q

Lecture 8: endo/exo and other diseases

eryhtromycin breath test

A

given radioactive erythrmoycin. metabolized by cyp3a4, and breathed out.

the more breathed out, the more it was metabolized

150
Q

Lecture 8: endo/exo and other diseases

surgery and proinfammatory cytokines

antiancer drugs and chemo

A

surgery ad inflammation showed decreased metabolism. presented by the erythromycin breathiest.

chemo drugs were metabolized less with increase degree of inflammation

151
Q

Lecture 8: endo/exo and other diseases

naproxen and RA

A

reduced metabolic cl and decreased protein binding

152
Q

Lecture 9: PKPD models and diabetes

ADME

A

A: not altered

D: altered albumin, reduced binding

M: liver dysfunction may develop

e: INCREASED GFR, THEN DECREASED GFR

153
Q

Lecture 9: PKPD models and diabetes

EFFECTS OF DIABETES ON PHENYTOIN PK

A

REDUCED PHENYTOIN PROTEIN BINDING, more free drug available, so they need less drug

154
Q

Lecture 9: PKPD models and diabetes

biologic turnovers

A

heart rate: fast msec

hormones, mrna: about an hour/hrs

cells: days tissue organs years

155
Q

Lecture 9: PKPD models and diabetes

direct effect models

biophase mpdela

A

de: rsponses follow along with plasma or biophase conc.

turnover models: responses controlled by turnover

156
Q

Lecture 9: PKPD models and diabetes

cox enzyme turnover after aspirin

A

aspirin inhibits platelets, and have to wait for turnover to get function again

157
Q

Lecture 9: PKPD models and diabetes

indirect response models

A
  1. inhibit k in (u)
  2. inhibit k out (n)
  3. stimulate kin (n)
  4. stimulation k out

PKPD II (4 decks)

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